Design and synthesis of the first thiophene thioglycosides

Article abstract of DOI:10.1080/00397910802590928

A novel reported method for preparation of the first thiophene thioglycosides via a one-pot reaction of sodium thiophenethiolate salts with 2,3,4,6-tetra-O-acetyl - D-gluco- and galactopyranosyl bromides has been studied. The sodium thiophenethiolate salts were prepared using sodium cyanoethylene thiolate salts. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802590928

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Design and Synthesis of the
First Thiophene Thioglycosides
Galal H. Elgemeie a , Shahinaz H. Elsayed a & Ashraf
S. Hassan a
a Faculty of Science , Chemistry Department,
Helwan University , Ain-Helwan, Helwan, Egypt
Published online: 15 Apr 2009.
To cite this article: Galal H. Elgemeie , Shahinaz H. Elsayed & Ashraf S. Hassan
(2009) Design and Synthesis of the First Thiophene Thioglycosides, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:10, 1781-1792, DOI: 10.1080/00397910802590928
To link to this article: http://dx.doi.org/10.1080/00397910802590928
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Synthetic Communications1, 39: 1781–1792, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802590928
Design and Synthesis of the First Thiophene
Thioglycosides
Galal H. Elgemeie, Shahinaz H. Elsayed, and Ashraf S. Hassan
Faculty of Science, Chemistry Department, Helwan University,
Ain-Helwan, Helwan, Egypt
Abstract: A novel reported method for preparation of the first thiophene thioglyco-
sides via a one-pot reaction of sodium thiophenethiolate salts with 2,3,4,6-tetra-
O-acetyl-a-D-gluco- and galactopyranosyl bromides has been studied. The sodium
thiophenethiolate salts were prepared using sodium cyanoethylene thiolate salts.
Keywords: Glycosides, halo sugars, sodium cyanoethylene thiolate salts,
thiophene thioglycosides
Thio-sugars have recently received interest as potential new
therapeutics.[1] Thus, new developments in the synthetic and medicinal
chemistry of thio-sugars are important for carbohydrate drug design.[2,3]
In recent reports from our laboratory, we described the preparation of
different novel functionalized pyridine thioglycosides, which revealed
antagonistic activity.[4,5] In an earlier brief communication, we had
already reported the use of dihydropyridine thioglycosides as substrates
or inhibitors in the protein glycosylation process.[6] These common
features encouraged us to develop a new straightforward route for synth-
esis of heterocyclic thioglycosides. In the present report, we describe the
synthesis of thiophene thioglycosides through reaction of sodium thio-
phenethiolates with a-halogeno sugars. As far as we know, this is the first
thiophene thioglycoside ring system to be reported in the literature.
Received August 24, 2008.
Address correspondence to Galal H. Elgemeie, Faculty of Science, Chemistry
Department, Helwan University, Ain-Helwan, Helwan, Egypt. E-mail: elgemeie@
yahoo.com
1781

1782
G. H. Elgemeie, S. H. Elsayed, and A. S. Hassan
It has been found that reaction of malononitrile 1a or ethyl cyano-
acetate 1b with carbon disulfide in the presence of sodium ethoxide gives
the sodium dithiolate salts 2a,b. Compounds 2 are readily monoalkylated
with 1 equivalent of phenacyl bromide or methyl iodide to give the
corresponding sodium salts of monoalkylated products 3 and 4 in good
yields. On acidification with hydrochloric acid, compounds 3 and 4 gave
the novel mercapto products 6 and 7, respectively. The structure of
compounds 6 and 7 were established on the basis of their elemental
analysis and spectral data infrared (IR), mass spectra (MS), and 1H
NMR). Compounds 3 and 4 reacted with 2,3,4,6-tetra-O-acetyl-a-D-
gluco- and galactopyranosyl bromides 5a,b in ethanol at room tempera-
ture to give the corresponding S-glycosides 8a,b and 9a,b, respectively,
in high yields. Compounds 8 and 9 could also be prepared by the reaction
of the thiols 6 and 7 with 5a,b in potassium hydroxide (KOH)–acetone at
room temperature for 15 h. We have hypothesized that the cis-(a) sugars
react by a simple Sn2 reaction to give the b-glycoside products.[7] The struc-
ture of the reaction products 8 and 9 were established and confirmed by
1
their elemental analysis and spectral data (IR and H NMR). Structure
8a is supported by its mass spectrum, its IR spectrum reveals the presence
of a CN band at 2224 cmꢀ1 and CO band at 1753 cmꢀ1, and its 1H NMR
spectrum shows the anomeric proton as a doublet at d 5.43 ppm with
a spin–spin coupling constant of 11.6 Hz, indicating the b-configuration.
The sodium a-cyanoketene thiolates 3 were cyclized by heating under
reflux in sodium ethoxide to give the corresponding sodium thiophene-
thiolates 10 and subsequently the novel 2-mercaptothiophenes 11. The
structures of compounds 11 were established on the basis of their elemental
analysis and spectral data (MS, IR, and 1H NMR). Upon alkylation with
halogenosugars 5, compounds 10 yielded the corresponding 2-(glycopyra-
nosylthio)thiophene derivative 12. Attempted preparation of 12 through
the reaction of thiophene-2-thiols 11 with halogenosugars 5 in KOH–
acetone was also successful in our hands. The structures of the reaction
products 12 were established and confirmed on the basis of their elemental
analysis and spectral data (IR and 1H NMR). Thus, the 1H NMR spectrum
for 12a showed the anomeric proton as a double at d 5.44 ppm with a spin–
spin coupling constant of 10.6 Hz, which corresponds to the diaxial orienta-
tion of H-10 and H-20 protons, indicating the b-configuration, whereas the
other six glucose protons resonated at d 3.87–5.33 ppm. The four-
acetyl groups appeared as four singlets at d 1.92–2.05 ppm.
In summary, we have achieved a novel synthesis of interesting thio-
phene thioglycosides by the reaction of the sodium thiophenethiolates
with a-halogenosugars. These glycosides are excellent starting materials
for the synthesis of other carbohydrate derivatives and for biological
evaluation studies.

First Thiophene Thioglycosides
EXPERIMENTAL
1783
All melting points were measured on a Gallenkamp melting-point appa-
ratus. The IR spectra were recorded (KBr disk) on a Perkin-Elmer 1650
Fourier transform (FT)–IR instrument. The 1H NMR spectra were
measured on a Varian 400-MHz spectrometer for solutions in dimethyl
sulfoxide (DMSO-d6) using Si(CH3)4 as an internal standard. Mass
spectra were recorded on a Varian MAT 112 spectrometer. Elemental
analyses were obtained from the Microanalytical Data Center at Cairo
University, Egypt.
Progress of the reactions was monitored by thin-layer chromato-
graphy (TLC) using aluminum sheets coated with silica gel F254 (Merck).
Viewing under a short-wavelength ultraviolet (UV) lamp effected detec-
tion. All evaporations were carried out under reduced pressure at 40ꢁC.
Sodium 1-Cyano-2-[(2-oxo-2-phenylethyl)thio]ethylene-2-thiolate (3a,b)
General Procedure
A solution of compounds 2a,b (0.01 mol) and phenacyl bromide (1.98 g,
0.01 mol) in methanol (20 ml) was stirred at rt for 2 h, the solution was
evaporated, and the formed solid product was collected by filtration.
Data
Compound 3a: Yellow, mp > 300ꢁC (EtOH), yield (79%). IR (KBr)
n
max=cmꢀ1 2202 (CN), 1641 (CO). C12H7N2S2ONa.
Compound 3b: Yellow, mp > 300ꢁC (EtOH), yield (75%). IR (KBr)
max=cmꢀ1 2187 (CN), 1670 (CO). C14H12NS2O3Na.
n
Sodium 1-Cyano-2-methylthioethylene-2-thiolate (4a,b)
General Procedure
A solution of compounds 2a,b (0.01 mol) and methyl iodide (1.4 g,
0.01 mol) in methanol (30 ml) was stirred at rt for 2 h. The solution was
evaporated, and the formed solid product was collected by filtration.
Data
Compound 4a: Yellow, mp > 300ꢁC (EtOH), yield (85%). IR (KBr)
n
max=cmꢀ1 2220 (CN). C5H3N2S2Na.

1784
G. H. Elgemeie, S. H. Elsayed, and A. S. Hassan
Compound 4b: Yellow, mp > 300ꢁC (EtOH), yield (80%). IR (KBr)
n
max=cmꢀ1 2215 (CN), 1730 (CO). C7H8NS2O2Na.
1-Cyano-2-mercapto-2-[(2-oxo-2-phenylethyl)thio]ethylene (6a,b)
General Procedure
A solution of compounds 3a,b in 20 ml ethanol was acidified with hydro-
chloric acid until it was neutral, and the formed solid product was col-
lected by filtration.
Data
Compound 6a: Orange, mp 165ꢁC (EtOH), yield (82%). IR (KBr) nmax
=
1
cmꢀ1 2222 (CN), 1627 (CO). H NMR (DMSO) d 4.35 (s, 2H, SCH2),
7.49–7.73 (m, 5H, C6H5), 8.71 (s, 1H, SH). C12H8N2S2O (Mþ ¼ 260) calcd.:
C, 55.38; H, 3.07; N, 10.76. Found: C, 55.2; H, 3.0; N, 10.4%.
Compound 6b: Yellow, mp 160ꢁC (EtOH), yield (79%). IR (KBr)
n
max=cmꢀ1 2211 (CN), 1720 (CO), 1694 (CO). 1H NMR (DMSO) d
1.35 (t, 3H, CH3), 4.00 (q, 2H, CH2), 4.33 (s, 2H, SCH2), 7.12–7.65 (m,
5H, C6H5), 9.56 (s, 1H, SH). C14H13NS2O3 (Mþ ¼ 307) calcd.: C,
54.70; H, 4.26; N, 4.55. Found: C, 54.5; H, 4.0; N, 4.3%.
1-Cyano-2-mercapto-2-methylthioethylene (7a,b)
General Procedure
A solution of compounds 4a,b in 20 ml ethanol was acidified with hydro-
chloric acid until it was neutral, and the formed solid product was
collected by filtration.
Data
Compound 7a: Orange, mp 100ꢁC (EtOH), yield (77%). IR (KBr)
1
n
max=cmꢀ1 2210 (CN). H NMR (DMSO) d 2.65 (s, 3H, SCH3), 10.71
(s, 1H, SH). C5H4N2S2 (Mþ ¼ 156), calcd.: C, 38.44; H, 2.58; N, 17.92.
Found: C, 38.1; H, 2.2; N, 17.8%.
Compound 7b: Orange, mp 80ꢁC (EtOH), yield (82%). IR (KBr)
n
max=cmꢀ1 2211 (CN), 1720 (CO). 1H NMR (DMSO) d 1.22 (t, 3H, CH3),
2.77 (s, 3H, SCH3), 4.09 (q, 2H, CH2), 11.67 (s, 1H, SH). C7H9NS2O2
(Mþ ¼ 203),calcd.:C, 41.35;H, 4.46;N, 6.89.Found:C, 41.2;H, 4.1;N, 6.6%.

First Thiophene Thioglycosides
1785
1-Cyano-2-[(2-oxo-2-phenylethyl)thio]-2-(20,30,40,60-tetra-O-acetyl-b-D-
gluco- or Galactopyranosylthio)ethylene (8a–d)
Method A
To a solution of compounds 3 (0.01 mol) in ethanol (30 ml), a solution of
5a,b (4.10 g, 0.01 mol) in acetone (20 ml) was added. The reaction mixture
was stirred at rt until completion (TLC, CHCl3–CH3OH, 9:1, 15 h) then
evaporated under reduced pressure, and the residue was washed with
distilled water to remove the formed sodium bromide. The resulting
products were crystallized from ethanol.
Method B
A solution of compounds 6 (0.01 mol) in aq. potassium hydroxide [0.56 g
(0.01 mol) in distilled water (6 ml)] was added to a solution of 5a,b (4.10 g,
0.01 mol) in acetone (30 ml). The reaction mixture was stirred at rt until
completion (TLC, CHCl3–CH3OH, 9:1, 15 h) then evaporated under
reduced pressure, and the residue was washed with distilled water to
remove the formed potassium bromide. The resulting products were
crystallized from ethanol.
Data
Compound 8a: Yellow, mp 100ꢁC (EtOH), yield (84%). IR (KBr)
n
max=cmꢀ1 2224 (CN), 1753 (CO), 1635 (CO). 1H NMR (DMSO) d
1.91–2.03 (4s, 12H, 4CH3CO), 3.90 (s, 2H, SCH2), 4.06–4.08 (m, 2H,
2H-60), 4.85 (t, 1H, H-50), 4.88–4.91 (m, 2H, H-40 and H-30), 5.34 (t,
1H, H-20), 5.43 (d, J1 -2 11.6 Hz, 1H, H-10), 7.48–7.74 (m, 5H, C6H5).
13C NMR d 18.0–20.0 (4 ꢂ CH3), 50.6 (CH2), 60.9 (CH2, C-60), 65.2
(C-40), 66.8 (C-20), 73.3 (C-30), 73.4 (C-50), 83.9 (C-10), 110.0 (CN),
115.0 (CN), 120.2–141.9 (C6H5), 155.5 (C-2), 160.4 (C-3), 168.3–185.4
(5 ꢂ CO). C26H26N2S2O10 (Mþ ¼ 590) calcd.: C, 52.87; H, 4.43; N, 4.74.
Found: C, 52.7; H, 4.3; N, 4.6%.
0
0
Compound 8b: Yellow, mp 90ꢁC (EtOH), yield (82%). IR (KBr)
n
max=cmꢀ1 2215 (CN), 1735 (CO), 1670 (CO). 1H NMR (DMSO) d
1.19 (t, 3H, CH3), 1.87–2.00 (4s, 12H, 4CH3CO), 3.79 (s, 2H, SCH2),
3.92 (q, 2H, CH2), 4.12–4.18 (m, 2H, 2H-60), 4.76 (t, 1H, H-50), 4.91–
4.99 (m, 2H, H-40 and H-30), 5.55 (t, 1H, H-20), 5.87 (d, J1 -2 11.6 Hz,
1H, H-10), 7.39–7.70 (m, 5H, C6H5).13C NMR d 19.7–21.8 (5 ꢂ CH3),
53.0 (SCH2), 58.3 (OCH2), 62.3 (CH2, C-60), 66.0 (C-40), 69.1 (C-20),
0
0

1786
G. H. Elgemeie, S. H. Elsayed, and A. S. Hassan
71.3 (C-30), 74.0 (C-50), 81.7 (C-10), 111.0 (CN), 119.0–138.5 (C6H5), 150.5
(C-2), 163.9 (C-3), 169.0–179.2 (6 ꢂ CO). C28H31NS2O12 (Mþ ¼ 637)
calcd.: C, 52.74; H, 4.90; N, 2.19. Found: C, 52.6; H, 4.8; N, 2.0%.
Compound 8c: Orange, mp 95ꢁC (EtOH), yield (80%). IR (KBr)
n
1.88–2.00 (4s, 12H, 4CH3CO), 3.87 (s, 2H, CH2), 4.00–4.10 (m, 2H,
max=cmꢀ1 2207 (CN), 1743 (CO), 1597 (CO). 1H NMR (DMSO) d
2H-60), 4.66 (t, 1H, H-50), 4.80–4.95 (m, 2H, H-40 and H-30), 5.21 (t,
1H, H-20), 5.40 (d, J1 -2 11.0 Hz, 1H, H-10), 7.22–7.70 (m, 5H, C6H5).
13C NMR d 18.9–20.5 (4 ꢂ CH3), 52.2 (SCH2), 61.5 (CH2, C-60), 67.0
(C-40), 69.2 (C-20), 71.6 (C-30), 75.0 (C-50), 81.5 (C-10), 110.8 (CN),
115.9 (CN), 119.0–138.9 (C6H5), 153.0 (C-2), 161.0 (C-3), 165.0–183.0
(5 ꢂ CO). C26H26N2S2O10 (Mþ ¼ 590) calcd.: C, 52.87; H, 4.43; N, 4.74.
Found: C, 52.7; H, 4.4; N, 4.7%.
0
0
Compound 8d: Yellow, mp 100ꢁC (EtOH), yield (78%). IR (KBr)
n
max=cmꢀ1 2213 (CN), 1752 (CO), 1668 (CO). 1H NMR (DMSO) d
1.15 (t, 3H, CH3), 1.80–2.08 (4s, 12H, 4CH3CO), 3.70 (s, 2H, SCH2),
3.90 (q, 2H, CH2), 4.10–4.20 (m, 2H, 2H-60), 4.66 (t, 1H, H-50), 4.70–
4.96 (m, 2H, H-40 and H-30), 5.60 (t, 1H, H-20), 5.80 (d, J1 -2 11.2 Hz,
1H, H-10), 7.49–7.79 (m, 5H, C6H5).13C NMR d 19.0–21.0 (5 ꢂ CH3),
51.9 (CH2), 56.7 (OCH2), 61.9 (CH2, C-60), 66.7 (C-40), 69.8 (C-20), 71.5
(C-30), 74.9 (C-50), 80.0 (C-10), 115.6 (CN), 118.5–139.2 (C6H5), 153.4
(C-2), 164.0 (C-3), 167.5–175.7 (6 ꢂ CO). C28H31NS2O12 (Mþ ¼ 637)
calcd.: C, 52.74; H, 4.90; N, 2.19. Found: C, 52.6; H, 4.8; N, 2.1%.
0
0
1-Cyano-2-methylthio-2-(20,30,40,60-tetra-O-acetyl-b-D-Gluco- or
Galactopyranosylthio)ethylene (9a–d)
Method A
Compounds 4a–b (0.01 mol) were treated as described for the preparation
of 8a–d.
Method B
Compounds 7a–b (0.01 mol) were treated as described for the preparation of
8a-d. The reaction was completed within 12h (TLC, CHCl3–CH3OH, 9:1).
Data
Compound 9a: Orange, mp 98ꢁC (EtOH), yield (76%). IR (KBr)
1
n
max=cmꢀ1 2209 (CN), 1735 (CO). H NMR (DMSO) d 1.20 (t, 3H,
CH3), 1.97–2.13 (4s, 12H, 4CH3CO), 2.62 (s, 3H, SCH3), 4.00–4.09 (m,

First Thiophene Thioglycosides
1787
2H, 2H-60), 4.85 (t, 1H, H-50), 4.88–4.91 (m, 2H, H-40 and H-30), 5.30 (t,
1H, H-20), 5.49 (d, J1 -2 11.2 Hz, 1H, H-10). 13C NMR d 18.9–21.0
(4 ꢂ CH3), 22.2 (CH3), 61.4 (CH2, C-60), 64.1 (C-40), 65.3 (C-20), 72.8
(C-30), 74.2 (C-50), 82.5 (C-10), 113.0 (CN), 117.0 (CN), 154.3 (C-2),
162.8 (C-3), 166.9–183.0 (4 ꢂ CO). C19H22N2S2O9 (Mþ ¼ 486) calcd.: C,
46.91; H, 4.55; N, 5.76. Found: C, 46.8; H, 4.5; N, 5.7%.
0
0
Compound 9b: White, mp 85ꢁC (EtOH), yield (81%). IR (KBr)
1
n
max=cmꢀ1 2219 (CN), 1753 (CO). H NMR (DMSO) d 1.24 (t, 3H,
CH3), 1.92–2.03 (4s, 12H, 4CH3CO), 2.44 (s, 3H, SCH3), 3.88 (q, 2H,
CH2), 4.01–4.24 (m, 3H, 2H-60 and H-50), 4.89–5.13 (m, 2H, H-40 and
H-30), 5.36–5.39 (d, 1H, H-20), 6.00–6.02 (d, 1H, H-10). 13C NMR d
17.5–20.1 (5 ꢂ CH3), 22.1 (CH3), 57.0 (OCH2), 61.9 (CH2, C-60), 66.6
(C-40), 68.9 (C-20), 73.0 (C-30), 75.8 (C-50), 80.5 (C-10), 112.6 (CN),
153.5 (C-2), 162.4 (C-3), 168.3–176.9 (5 ꢂ CO). C21H27NS2O11
(Mþ ¼ 533) calcd.: C, 47.27; H, 5.10; N, 2.62. Found: C, 47.0; H, 5.0;
N, 2.4%.
Compound 9c: Yellow, mp 90ꢁC (EtOH), yield (75%). IR (KBr)
1
n
max=cmꢀ1 2218 (CN), 1730 (CO). H NMR (DMSO) d 1.90–2.10 (4s,
12H, 4CH3CO), 2.32 (s, 3H, SCH3), 4.05–4.10 (m, 2H, 2H-60), 4.80 (t,
1H, H-50), 4.80–4.90 (m, 2H, H-40 and H-30), 5.44 (t, 1H, H-20), 5.55
(d, J1 -2 11.2 Hz, 1H, H-10). 13C NMR d 19.2–21.7 (4 ꢂ CH3), 22.9
(CH3), 61.9 (CH2, C-60), 64.8 (C-40), 65.9 (C-20), 72.4 (C-30), 74.9
(C-50), 82.4 (C-10), 114.7 (CN), 116.7 (CN), 155.9 (C-2), 163.7 (C-3),
165.9–181.5 (4 ꢂ CO). C19H22N2S2O9 (Mþ ¼ 486) calcd.: C, 46.91; H,
4.55; N, 5.76. Found: C, 46.8; H, 4.5; N, 5.7%.
0
0
Compound 9d: Buff, mp 80ꢁC (EtOH), yield (78%). IR (KBr)
1
n
max=cmꢀ1 2210 (CN), 1753 (CO). H NMR (DMSO) d 1.13 (t, 3H,
CH3), 1.85–2.00 (4s, 12H, 4CH3CO), 2.60 (s, 3H, SCH3), 3.77 (q, 2H,
CH2), 4.11–4.33 (m, 3H, 2H-60 and H-50), 4.77–5.10 (m, 2H, H-40 and
H-30), 5.22–5.40 (d, 1H, H-20), 6.04–6.09 (d, 1H, H-10). 13C NMR d
18.1–21.6 (5 ꢂ CH3), 23.0 (CH3), 58.2 (OCH2), 62.5 (CH2, C-60), 65.3
(C-40), 67.5 (C-20), 72.1 (C-30), 74.0 (C-50), 79.5 (C-10), 111.0 (CN),
154.0 (C-2), 161.5 (C-3), 167.7–179.0 (5 ꢂ CO). C21H27NS2O11 (Mþ ¼ 533)
calcd.: C, 47.27; H, 5.10; N, 2.62. Found: C, 47.2; H, 5.0; N, 2.5%.
Sodium 4-Amino-5-benzoylthiophene-2-thiolate (10a,b)
General Procedure
A solution of compounds 3a,b (0.01 mol) was refluxed with sodium
ethoxide (0.23 g, 0.01 mol) in ethanol (20 ml) for 2 h, the solution was
evaporated, and the formed solid product was collected by filtration.

1788
G. H. Elgemeie, S. H. Elsayed, and A. S. Hassan
Data
Compound 10a: Brown, mp > 300ꢁC (EtOH), yield (80%). IR (KBr)
n
max=cmꢀ1 3453 (NH2), 2225 (CN), 1676 (CO). C12H7N2S2ONa.
Compound 10b: Brown, mp > 300ꢁC (EtOH), yield (78%). IR (KBr)
max=cmꢀ1 3430 (NH2), 1627 (CO). C14H12NS2O3Na.
n
4-Amino-5-benzoyl-2-mercaptothiophene (11a,b)
General Procedure
A solution of compounds 3a,b (0.01 mol) was refluxed with sodium ethox-
ide (0.23 g, 0.01 mol) in ethanol (20 ml) for 2 h, then poured on cold water
and treated with hydrochloric acid until it was neutral. The formed solid
products were collected by filtration and recrystallized from ethanol.
Data
Compound 11a: Yellow, mp 100ꢁC (EtOH), yield (78%). IR (KBr)
1
n
max=cmꢀ1 3418 (NH2), 2211 (CN), 1655 (CO). H NMR (DMSO) d
4.43 (m, 2H, NH2), 7.41–7.55 (m, 5H, C6H5), 8.13 (s, 1H, SH).
C12H8N2S2O (Mþ ¼ 260) calcd.: C, 55.36; H, 3.09; N, 10.76. Found: C,
55.1; H, 3.0; N, 10.6%.
Compound 11b: Brown, mp 110ꢁC (EtOH), yield (79%). IR (KBr)
1
n
max=cmꢀ1 3419 (NH2), 1725 (CO), 1619 (CO). H NMR (DMSO) d
1.15 (t, 3H, CH3), 3.97 (q, 2H, CH2), 4.80 (m, 2H, NH2), 7.33–7.87 (m,
5H, C6H5), 9.15 (s, 1H, SH). C14H13NS2O3 (Mþ ¼ 307) calcd.: C,
54.70; H, 4.26; N, 4.55. Found: C, 54.6; H, 4.1; N, 4.4%.
4-Amino-5-benzoyl-2-(20,30,40,60-Tetra-O-acetyl-b-D-Gluco- or
Galactopyranosylthio)thiophene (12a–d)
Method A
To a solution of compounds 10a,b (0.01 mol) in ethanol (30 ml), a solu-
tion of 5a,b (4.10 g, 0.01 mol) in acetone (20 ml) was added. The reaction
mixture was stirred at rt. until completion (TLC, CHCl3–CH3OH, 9:1,
14 h) and then evaporated under reduced pressure, and the residue was
washed with distilled water to remove the formed sodium bromide. The
resulting product was crystallized from ethanol.

First Thiophene Thioglycosides
1789
Method B
A solution of compounds 11a,b (0.01 mol) in aq. potassium hydroxide
[(0.56 g, 0.01 mol) in distilled water (6 ml)] was added to a solution of
5a,b (4.10 g, 0.01 mol) in acetone (30 ml). The reaction mixture was stirred
at rt until completion (TLC, CHCl3–CH3OH, 9:1, 14 h), and then evapo-
rated under reduced pressure, and the residue was washed with distilled
water to remove the formed potassium bromide salt. The resulting
product was crystallized from ethanol.
Data
Compound 12a: Yellow, mp 88ꢁC (EtOH), yield (80%). IR (KBr)
1
n
max=cmꢀ1 3430 (NH2), 2220 (CN), 1754 (CO), 1650 (CO). H NMR
(DMSO) d 1.92–2.05 (4s, 12H, 4CH3CO), 3.87–4.29 (m, 3H, 2H-60 and
H-50), 4.91–5.01 (m, 2H, H-40 and H-30), 5.11–5.33 (m, 2H, H-20), 5.44
(d, J1 -2 10.6 Hz, 1H, H-10), 7.24–7.83 (m, 5H, C6H5), 8.42 (s, 2H,
0
0
13
NH2). C NMR d 20.8–21.4 (4 ꢂ CH3), 61.9 (CH2, C-60), 68.7 (C-40),
69.5 (C-20), 73.7 (C-30), 74.7 (C-50), 85.0 (C-10), 111.0 (CN), 119.4–144.0
(C6H5), 160.6–187.9 (5 ꢂ CO). C26H26N2S2O10 (Mþ ¼ 590) calcd.: C,
52.88; H, 4.43; N, 4.74. Found: C, 52.8; H, 4.3; N, 4.7%.
Compound 12b: Brown, mp 85ꢁC (EtOH), yield (84%). IR (KBr)
max=cmꢀ1 3451 (NH2), 1754 (CO), 1670 (CO). H NMR (DMSO) d
1
n
1.24 (t, 3H, CH3), 1.94–2.05 (4s, 12H, 4CH3CO), 3.88 (q, 2H, CH2),
4.11–4.24 (m, 3H, 2H-60 and H-50), 4.63–4.98 (m, 2H, H-40 and H-30),
5.29–5.41 (t, 1H, H-20), 5.67–5.75 (d, 1H, H-10), 7.21–7.70 (m, 5H,
C6H5), 8.22 (m, 2H, NH2). 13C NMR d 19.2–20.9 (4 ꢂ CH3), 23.3
(CH3), 56.0 (OCH2), 60.5 (CH2, C-60), 67.9 (C-40), 69.9 (C-20), 74.9 (C-
30), 76.2 (C-50), 83.2 (C-10), 118.2–139.0 (C6H5), 163.2–185.3 (6 ꢂ CO).
C28H31NS2O12 (Mþ ¼ 637) calcd.: C, 52.74; H, 4.90; N, 2.19. Found:
C, 52.7; H, 4.8; N, 2.1%.
Compound 12c: Yellow, mp 84ꢁC (EtOH), yield (83%). IR (KBr)
n
max=cmꢀ1 3400–3330 (NH2), 2225 (CN), 1739 (CO), 1670 (CO). 1H
NMR (DMSO) d 1.90–2.00 (4s, 12H, 4CH3CO), 3.99–4.20 (m, 3H, 2H-
60 and H-50), 4.88–5.00 (m, 2H, H-40 and H-30), 5.12–5.33 (m, 2H, H-
20), 5.44 (d, 1H, H-10), 7.24–7.83 (m, 5H, C6H5), 8.42 (s, 2H, NH2). 13C
NMR d 19.6–22.0 (4 ꢂ CH3), 60.5 (CH2, C-60), 67.9 (C-40), 70.3 (C-20),
72.8 (C-30), 75.2 (C-50), 83.4 (C-10), 114.5 (CN), 119.0–147.0 (C6H5),
161.0–186.2 (5 ꢂ CO). C26H26N2S2O10 (Mþ ¼ 590) calcd.: C, 52.88; H,
4.43; N, 4.74. Found: C, 52.8; H, 4.4; N, 4.7%.
Compound 12d: Yellow, mp 86ꢁC (EtOH), yield (78%). IR (KBr)
n
max=cmꢀ1 3450, 3370 (NH2), 1730 (CO), 1650 (CO). 1H NMR (DMSO)

1790
G. H. Elgemeie, S. H. Elsayed, and A. S. Hassan
Scheme 1. Reaction of sodium cyanoethylene sodium salts with halo sugars.
d 1.10 (t, 3H, CH3), 1.90–2.14 (4s, 12H, 4CH3CO), 3.90 (q, 2H, CH2),
4.08–4.13 (m, 3H, 2H-60 and H-50), 4.65–4.90 (m, 2H, H-40 and H-30),
5.17–5.38 (t, 1H, H-20), 5.55–5.87 (d, 1H, H-10), 7.54–7.90 (m, 5H,
C6H5), 8.18 (m, 2H, NH2). 13C NMR d 18.5–21.3 (4 ꢂ CH3), 22.7
(CH3), 55.5 (OCH2), 61.3 (CH2, C-60), 66.6 (C-40), 68.5 (C-20), 73.5 (C-
30), 75.9 (C-50), 82.6 (C-10), 119.9–141.0 (C6H5), 162.9–184.9 (6 ꢂ CO).

First Thiophene Thioglycosides
1791
Scheme 2. Synthesis of thiophene thioglycosides.
C28H31NS2O12 (Mþ ¼ 637) calcd.: C, 52.74; H, 4.90; N, 2.19. Found: C,
52.7; H, 4.9; N, 2.1%.
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